Penny, Amy, and Bernadette are in a public toilet. Amy is in one stall talks to Penny who is in the adjoining one. Amy explains that her previous trips to the toilet have mostly been about excreting, but now she can socialize too.

Penny doesn't enjoy this socializing activity too much as she presumably suffers from bladder shyness. Next, the girls proceed to a shoe store, where Bernadette announces that she and Howard have been invited by Priya to dine with her and Leonard. Amy assumes Priya plans to test Bernadette's loyalty to the group but Amy wants Bernadette to attend the dinner as a double agent.

Code Name: Wildebeest.

Amy is hanging out at Penny's apartment and gets a text confirming that Bernadette is at Raj's apartment dining with Priya, Leonard, and Howard. Bernadette soon alerts Amy and Penny about a snide comment Priya made about Penny's acting career. In retaliation, they lie about Penny shooting a movie with Angelina Jolie in Prague which will be shown in 3D. Leonard is surprised Penny didn't tell him this fact. Priya asks why he is surprised when he doesn't spend time with Penny, his ex-girlfriend. Leonard, who is now trapped between a rock and a hard place, is at a loss for words, but finally says he wasn't surprised, but "befuddled". Bernadette announces Penny is also dating an astronaut after she misreads a text saying "architect" from Amy and Penny.

Sheldon is emulating three person chess

At apartment 4A, Sheldon is emulating three people as he tests out his three-person chess when, suddenly, Raj knocks on the door and says he needs a hug. Sheldon makes the excuse that he has company (his other two selves). After some deliberation, he lets Raj in who tells him he has received a new drug his friend claims to be "the next big thing" for people with social anxiety. Raj is worried that the side effects will affect his brain, which is a very important tool in his field. Sheldon reassures him as he believes Raj isn't that smart.

Bernadette talks at the phone with Amy in Raj's bathroom

Back at Raj's place, Howard is curious about how Penny met an astronaut. Bernadette tries to answer his question, but soon the lies falls apart and she gradually becomes crankier. Bernadette then heads to the toilet and calls Penny and Amy. She tells them about her dilemma about the lie falling apart. Bernadette mentions Leonard is going to India to meet Priya's parents.

Raj and Sheldon go out to a coffee shop to test out the effects of the drug. Raj approaches a girl and stares at her silently for a moment. Eventually he is able to talk to her and they hit it off quite admirably. Sheldon takes his eyes off Raj for a moment and, when he looks at him again, Raj is already stripping. The woman leaves as Raj becomes completely nude. The drug removed all his social inhibitions.

Leonard, Sheldon and Howard play three-person chess

Back at Raj's, Bernadette asks Priya about her and Leonard's trip to India. After establishing Priya is not getting engaged to Leonard, Bernadette tells Priya she is going to the bathroom but her true intention is to update Penny and Amy. Priya notes that she has been in there a lot this evening and asks if she's okay. Bernadette breaks down and storms off, with Howard following. Priya is at a loss for words at her actions and Leonard says "I think the word you are looking for is 'befuddled.'"

The final scene shows Leonard, Sheldon, and Howard playing a confusing game of three-person chess, and Raj, who is completely naked, still under the effects of the drug.

The TV Critic: "I liked the simple way that situation unfolded. Penny suggested the lie in a simple flick of resentment but the less savvy Amy and Bernadette foolishly took her seriously. The transformation of Amy into a "typical" girl remains fun...The writers lost focus here and presented a fairly mediocre story. However the strong arc plot they have built up for the characters prevented this from feeling too irrelevant."[2]

When Sheldon is working on his three-person chess game, but is interrupted by a lonely Raj, he announces that he has company and later speaks to an empty chair for an aside. Apparently, he has created imaginary opponents to test his chess variant. In "The Porkchop Indeterminacy", Sheldon's twin sister Missy mentioned his imaginary friends during his childhood, to what Sheldon corrects her saying they were imaginary colleagues.

Penny is the only one who does not share any scenes with the guys in this episode.

Before Raj leaves the apartment, he decides to wear his blue windbreaker which portrays his sadness. He then encounters Sheldon (wearing orange) at his apartment and theorizes that orange should resemble loneliness since it does not rhyme with any word.

A few episodes before "The Cohabitation Formulation", Priya states to Raj that if you eat beef, you will have to live with cows for three months and drink their urine but he disbelieves this portion of the Hindu code. In this episode, Raj tells Sheldon that he is taking medication that has a beta-blocker with an extract from cow's urine.

While Howard, Leonard, Priya, and Amy consider it implausible for Penny to date an astronaut causing Bernadette grief, Howard later becomes an actual astronaut in the next season.

First episode to show Bernadette's short temper and aggressive nature, a running gag in future episodes.

Sheldon: Actually I was wondering if I could add a third new chess piece. How do you feel about Prince Joey? The king's feeble minded but well-meaning cousin... The fun thing about Prince Joey is every time he moves, there's a one in five chance he'll kill himself.